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Fever Of Unknown Origin

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Contains 17 clinical situations of prolonged fever and discussion of various differential diagnosis based on them. Also gives the key points in the diagnosis of a prototype diagnosis and the usefulness of a relevant investigation modality in identifying these conditions. This power point presentaion is based on the chapter in Harrison's Text Book on Internal Medicine chapter on Fever of Unknown Origin

Contains 17 clinical situations of prolonged fever and discussion of various differential diagnosis based on them. Also gives the key points in the diagnosis of a prototype diagnosis and the usefulness of a relevant investigation modality in identifying these conditions. This power point presentaion is based on the chapter in Harrison's Text Book on Internal Medicine chapter on Fever of Unknown Origin


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Fever Of Unknown Origin

  1. 1. FEVER OF UNKNOWN ORIGIN<br />Dr. S. Aswini Kumar. MD.<br />Professor of Medicine,<br />Medical College Hospital, <br />Thiruvananthapuram.<br />
  2. 2. Definition:<br />Fever of unknown origin (FUO) was defined by Petersdorf and Beeson in 1961 as <br />temperatures higher than 38.3°C on several occasions, a duration of fever of more than 3 weeks, and failure to reach a diagnosis despite 1 week of in-patient investigation. <br />
  3. 3. New classification:<br />Durack and Street have proposed a new system for classification of FUO: <br />classic FUO, <br />nosocomial FUO, <br />neutropenic FUO, and <br />FUO associated with HIV infection <br />
  4. 4. Classic PUO:<br />This category corresponds closely to the earlier definition of FUO ,butthe new definition is broader, <br />stipulating three outpatient visits or 3 days in the hospital without elucidation of a cause or 1 week of "intelligent and invasive" ambulatory investigation. <br />
  5. 5. 1. Diagnosis ?<br />A 50 year old man was admitted with fever of three weeks duration. On examination there was hepatosplenomegaly. Routine urine and blood examinations were normal. Widal test and Mantouex test were negative. Chest X-Ray and HIV were negative. Liver biopsy showed presence of granulomas<br />
  6. 6. Granulomatous hepatitis<br />Systemic Sarcoidosis<br />Miliary tuberculosis<br />Lymphomas<br />Wegener’s<br />Brucellosis<br />Histoplasmosis<br />Shistosomiasis<br />
  7. 7. Systemic Sarcoidosis<br />
  8. 8. Liver Biopsy in FUO<br />Mehngini/Vim’s/True cut needle<br />To be cultured and retained<br />
  9. 9. 2. Diagnosis?<br />A 45 year old man was admitted to the CCU with acute MI, thrombolysed and reperfused, but then went into persistent hypotension following a cardiac arrest. He developed fever on Day 5. Routine blood investigation showed a polymorpho-nuclear leucocytosis. Blood culture was diagnostic<br />
  10. 10. Nosocomial FUO:<br />“In nosocomialFUO, a temperature of ³38.3°C develops on several occasions in a hospitalized patient who is receiving acute care and in whom infection was not manifest or incubating on admission.<br />Three days of investigation, including at least 2 days' incubation of cultures, is the minimum requirement for this diagnosis”<br />
  11. 11. Nosocomial FUO<br />Post Myocardial infarction syndrome<br />Pulmonary thromboembolism<br />Occult Nosocomial infection<br />Transfusion related viral infections<br />Infected intra-vascular lines<br />Catheter related infections<br />Drug related fever<br />
  12. 12. Blood Culture in FUO<br />Method<br />Rapid identification<br />
  13. 13. Dressler’s Syndrome<br />
  14. 14. 3. Diagnosis?<br />A 30 year old farmer working in a diary farm in Tamil Nadu was admitted to the ward with low grade fever and evening rise of temperature. On examination there was generalized lymphadenopathy and hepato-splenomegaly. Blood routine, Chest X-ray PA view & Blood Widal test were negative<br />
  15. 15. Systemic bacterial infections<br />Brucellosis<br />Typhoid fever<br />Leptospirosis<br />Campylobacter infection<br />Meningococcemia<br />Lyme’s disease<br />Legionaire’s disease<br />
  16. 16. Brucellosis<br />
  17. 17. Serological Tests<br />Widal Test<br />Methodology<br />
  18. 18. 4. Diagnosis?<br />A 49 year old college Professor came with pain in the right loin and fever of one month duration. Loss of appetite and loss of weight were present. He was investigated for UTI. Repeated URE and urine cultures were negative. Renal angle was dull but non tender. CT scan of abdomen was diagnostic<br />
  19. 19. Malignancies<br />Renal cell carcinoma<br />Pancreatic cancer<br />Cancer colon<br />Lymphoma <br />Leukemia<br />Hepatoma<br />Sarcoma<br />
  20. 20. Renal Cell carcinoma<br />
  21. 21. Ultra-sound scan in FUO<br />Look at<br />USS Abd in RCC<br />
  22. 22. 5. Diagnosis?<br />A 14 year old boy was admitted with high grade fever and pallor. On examination no hepatosplenomegaly, lymphadenopathy or bone tenderness were present. The blood counts were as follows: Hb 8gm%, TC 3800, P8 L86 E4 M2, ESR 20 mm in 1st hr. Platelet count 2.5 lakhs, BT 1’30” CT 3’30”<br />
  23. 23. Neutropenic FUO:<br />NeutropenicFUO is defined as a temperature of 38.3°C on several occasions in a patient whose neutrophil count is <500/L or is expected to fall to that level in 1–2 days.<br /> The diagnosis of neutropenic FUO is invoked if a specific cause is not identified after 3 days of investigation, including at least 2 days' incubation of cultures<br />
  24. 24. Neutropenic FUO<br />Focal infections <br />Systemic infections<br />Bacterial infections <br />Fungal infections<br />Catheter infections <br />Perianal infections <br />Infections due to HSV and CMV <br />
  25. 25. Cyclic Neutropenia<br />
  26. 26. Bone Marrow studies<br />Bone marrow aspiration<br />Yields<br />
  27. 27. 6. Diagnosis?<br />A 55 year old woman presented with high grade remittent fever and severe pain in the right shoulder. No pallor/lymphadenopathy. Liver was palpable 8 cm below the costal margin. Soft and non tender. X ray chest and fluoroscopy showed elevated right hemi diaphragm with reduced movements<br />
  28. 28. Pus somewhere<br />Pancreatic abscess<br />Pelvic inflammatory disease<br />Prostatic abscess<br />Tubo-ovarian abscess<br />Sub diaphragmatic abscess<br />Liver abscess<br />Dental abscess<br />
  29. 29. Pancreatic Abscess<br />
  30. 30. CT Scan as a tool in FUO<br />Pacreatic Abscess in CT<br />Superior to USS Abd<br />
  31. 31. 7. Diagnosis?<br />A 19 year old girl was diagnosed to have infective endocarditis, because she had fever, pallor and systolic murmur. Repeated blood cultures were negative and she did not improve with antibiotics given for SBE. After 4 weeks she was skin and bones and still febrile. This time CXR was diagnostic<br />
  32. 32. Tuberculosis<br />Miliary tuberculosis<br />Pulmonary Tuberculosis <br />Tuberculous pleural effusion<br />Tuberculous pericarditis<br />Intestinal tuberculosis<br />TB Lymphadenitis<br />Renal tuberculosis<br />
  33. 33. Miliary Tuberculosis<br />
  34. 34. Chest X-Ray in FUO<br />Diagnosis from CXR<br />Encysted Empyema in CXR<br />
  35. 35. 8. Diagnosis?<br />A 25 year-old woman was admitted with a suspicion of rheumatic fever. A mid-diastolic murmur was audible to 4 out of 11 post graduate doctors in medicine who examined the case. ECG did not show RVH nor was there any straightening of the left border of heart in the chest X-ray PA view.<br />
  36. 36. Cardiac Causes of FUO<br />Left atrial myxoma<br />Sub acute bacterial endocarditis<br />Prosthetic valve endocarditis<br />Aortic dissection<br />Tuberculous pericardial effusion<br />Chronic constrictive Pericarditis<br />Post myocardial infarction syndrome<br />
  37. 37. Left atrial myxoma<br />
  38. 38. ECHO in FUO<br />Diagnosis by ECHO<br />Vegetation in ECHO<br />
  39. 39. 9. Diagnosis?<br />A 45 year old man , who returned from Mumbai where he was working as a taxi driver for the past twelve years. He was admitted with low grade fever and cervical lymphadenopathy. He was undergoing treatment from various hospitals for irritable bowel syndrome since last six months<br />
  40. 40. HIV associated FUO:<br />“HIV associated FUO is defined by a temperature of 38.3C (101F) on several occasions over a period of 4 weeks for outpatients or 3 days for hospitalized patients with HIV infection. <br />This diagnosis is invoked if appropriate investigation over 3 days, including 2 days’ incubation of cultures, reveals no source.”<br />
  41. 41. Human Inmmuno Deficiency<br />HIV Infection as such<br />Pulmonary Tuberculosis<br />Pneumocystis Infection<br />Toxoplasmosis<br />Cytomegalovirus infection<br />M. Avium or M. Intracellulare<br />Non-Hodgkin’s Lymphoma<br />
  42. 42. Toxoplasmosis<br />
  43. 43. HIV testing in FUO<br />IV Generation Screening<br />CD4 counts and HIV RNA copies<br />
  44. 44. 10. Diagnosis?<br />A 15 year old boy was admitted with history of fever of seven days duration. Clinical examination showed a generalized maculopapular rash and generalized lymphadenopathy, hepatosplenomegaly. All the routine investigations for a underlying bacterial infection were found negative<br />
  45. 45. Viral Infections<br />Infectious Mononucleosis<br />Hepatitis A B C D and E<br />Ebstein Barr virus infection<br />Cytomegalovirus infection<br />Parvovirus infection<br />Dengue hemorrhagic fever<br />Lymphocytic chorio-meningitis<br />
  46. 46. Cytomegalovirus infection<br />
  47. 47. Virology in FUO<br />Availability limitation<br />H1N1 Serology<br />
  48. 48. 11. Diagnosis?<br />A sixty year old man was admitted with history of fever, headache and vomiting. O/E neck stiffness was present. Initial CSF study showed 50cells P60 L40. Repeat LP showed protein 45mg% and sugar 80mg%. Patient did not improve much in spite of combined regimen with antibiotics and ATT<br />
  49. 49. Fungal Infections<br />Cryptococcal meningitis<br />Aspergillosis<br />Blastomycosis<br />Candidiasis<br />Histoplasmosis<br />Mucormycosis<br />Sporotrichosis<br />
  50. 50. Cryptococcal meningitis<br />
  51. 51. CSF Study in FUO<br />Highly informative<br />Any time investigation<br />
  52. 52. 12. Diagnosis?<br />A 20 year-old college student ,while on an All India Tour on motor cycle , was involved in a road traffic accident and suffered from multiple fractures of the femur which necessitated multiple blood transfusions. He developed high grade fever with chills and rigor after one week<br />
  53. 53. Parasitic Infections<br />Malaria<br />Amoebiasis<br />Leishmaniasis<br />P.carinii<br />Toxoplasmosis<br />Trichinosis<br />Strongiloidiasis<br />
  54. 54. Malaria<br />
  55. 55. Peripheral Smear in FUO<br />Simple bed side test<br />Peripheral smear in Leukemia<br />
  56. 56. 13. Diagnosis?<br />A 14 year old girl was suffering from recurrent generalized seizures. She was put on Phenobarbitone and Dilantin sodium for the same. She had persistent low grade fever, but no lymph node enlargement or hepatosplenomegaly. Blood examination showed evidence of megaloblastic anemia<br />
  57. 57. Drug fever/Non-infectious causes<br />Gout<br />Hematoma<br />Haemolysis<br />Cirrhosis of liver<br />Pulmonary emboli<br />Subacute thyroiditis<br />Tissue infarction<br />
  58. 58. Gout<br />
  59. 59. Biochemical Tests in FUO<br />Blood Chemistry<br />Tests to be ordered<br />
  60. 60. 14. Diagnosis?<br />A 30 year old police man came with recurrent episodes of abdominal pain and abdominal distension, loss of weight and loss of appetite. He had fistulectomy on 2 occasions. He was weighing only 32kg. Pallor +. Abdomen was soft. No hepato-splenomegaly.Colonoscopy was diagnostic<br />
  61. 61. Inflammatory Bowel Diseases<br />Crohn’s disease<br />Ulcerative colitis<br />Intestinal tuberculosis<br />Cholangitis<br />Cholecystitis<br />Mesenteric adenitis<br />Osteomyelitis<br />
  62. 62. Crohn’s disease<br />
  63. 63. Tissue Biopsy in FUO<br />Biopsy specimens<br />Advantages & limitations<br />
  64. 64. 15. Diagnosis?<br />A 75 year-old man came with fever and headache of 4 months duration. He had generalized body aches and pains.He was admitted to ophthalmic hospital one week before for complaints of sudden loss of vision in one eye. Routine investigations were negative except for a high ESR<br />
  65. 65. Connective tissue disorders<br />Temporal arteritis<br />Adult Still’s disease<br />Systemic lupus erythematosus<br />Rheumatoid arthritis<br />Poly-arteritisnodosa<br />Mixed connective tissue disease<br />Relapsing polychondritis<br />
  66. 66. Temporal arteritis<br />
  67. 67. Collagen Work up in FUO<br />ANA Profile<br />Direct Immunoflourescence<br />
  68. 68. 16. Diagnosis?<br />A 45 year old lady came with generalized weakness, loss of weight and frequent loose stools. She always felt hot in her body and sweated excessively. Fine abnormal movements were present in the fingers. She had a fast heart rate which was out of proportion to her body temperature <br />
  69. 69. Metabolic/endocrine disorders<br />Hyperthyroidism<br />Central causes<br />Cerebrovascular accidents<br />Encephalitis<br />Brain tumor<br />Hypothalamic dysfunction<br />Pheochromocytoma<br />
  70. 70. Hyperthyroidism<br />
  71. 71. Endocrine Tests in FUO<br />Array of tests<br />Cover the system<br />
  72. 72. 17. Diagnosis?<br />A 19 year-old nursing student attending the OPD complained that she had high grade fever on several occasions in a day for past four weeks. She was unable to attend the ward examinations during this period because of the persistent fever. In between the fevers she was apparently healthy<br />
  73. 73. Miscellaneous Disorders<br />Factitious fever<br />Habitual hyperthermia<br />Afebrile FUO (<38.3oC)<br />Exaggerated circadian rhythm<br />Hysterical Fever<br />MaliganantHyperthermia<br />Neuroleptic Malignant Syndrome<br />
  74. 74. Habitual hyperthermia<br />
  75. 75. Conclusions<br />
  76. 76. Thank You for the patient listening<br />

Notas del editor

  • An underestimated reason is factitious fever. Patients frequently are women that work, or have worked, in the medical field and have complex medical historiesHabitual Hyperthermia is a condition of unknown cause that occurs in young females, characterized by body temperatures of 99° F to 100.5° F regularly or intermittently for years. No organic cause can be foundAfebrile FUO (&lt;38.3oC) Means the temperature recorded is always less than (&lt;38.3oC). However patient always complaints of feverishnessExaggerated circadian rhythm: The normal person has an evening rise of temperature which is not normally apparent. This becomes evidentHysterical Fever: Patient in his or subconcious mind is thinking that he is always having feverMalignant hyperthermia is a rare life-threatening condition that is triggered by exposure to certain drugs used for general anesthesia (specifically all volatile anesthetics), nearly all gas anesthetics, and the neuromuscular blocking agent succinylcholineNeuroleptic malignant syndrome (NMS) is a life threatening, although rare neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs. It generally presents with muscle rigidity, fever, autonomic instability
  • Patients with continuous low grade fever lasting months or years.They are otherwise physically well frequently present perplexing problems to the clinician. Even after prolonged fruitless investigation one hesitates in most cases of this nature to dismiss the matter lightly lest some unrecognized or occult lesion be present. Yet few physicians have the opportunity and few patients the time and money necessary for investigation and observation over long periods. The patient with such a condition often becomes dissatisfied with the negative results of repeated examinations by his own physician Then commences a tour to a long series of physicians, as illustrated in the following reports of cases. As often happens, each physician approaches the case from a different point of view and arrives at a different conclusionThe patient is alarmed by the array of suggested diagnostic possibilities and, if not already neurotic, may become so.